Selenium deficiency leads to decreased concentration and therefore function of selenoenzymes. Some consequences of this in animals are increased susceptibility to infections, to toxicity of certain drugs and chemicals, and to damage by other nutritional deficiencies. There is evidence for selenium deficiency of varying severity in human populations in Asia, Europe, and Africa. In addition, some people in the U.S. with cirrhosis appear to be selenium deficient. This project aims to acquire the knowledge necessary to assess the need for selenium supplementation of populations and individuals and to formulate cost-effective supplements. In the previous grant period three clinical studies were completed. One, carried out in a selenium-deficient population in China, demonstrated that selenoprotein P concentration was superior to glutathione peroxidase activity as a plasma index of selenium nutritional status. It indicated that the present recommended dietary allowance for selenium is too low and showed that bioavailability of commonly used forms of the element vary widely. A study of healthy subjects in the U.S. demonstrated that selenium supplements did not increase either plasma selenoprotein, indicating that the subjects were selenium replete. Plasma selenium increased but the increase was different with each form of selenium given. An equation was derived that related increase in plasma selenium concentration to selenomethionine intake. The third study showed that some patients in the U.S. with severe cirrhosis are selenium deficient, presumably because they are unable to metabolize dietary selenomethionine. In the coming grant period we propose two studies in China, where a selenium-deficient population is available. One will determine the selenium requirement of healthy subjects based on plasma selenoprotein P and the other will determine the bioavailability of forms of selenium commonly used as supplements. A study of U.S. patients with cirrhosis is proposed to assess the occurrence of selenium deficiency over the disease spectrum and to determine the form and dose of selenium needed to repair it. Finally, characterization of the small-molecule transportform of selenium in plasma and development of an assay for it will be carried out with the expectation that it will serve as a superior index of selenium status. All these studies are aimed at facilitating efforts to determine the health effects of selenium deficiency and to guide supplementation of the element when that is needed.